Current Research
I am interested in the molecular basis of nervous system development in vertebrates, especially transcriptional regulation (both genetic and epigenetic) in neurogenesis and paediatric brain tumours. The Scotting lab is a young and internationally diverse group with graduate students coming from all corners of the globe. The current group includes 7 graduate students, 5 of whom are from overseas.
Specific Areas of Research:
Molecular mechanisms of nervous system formation
These studies utilise a range of molecular and cellular approaches such as in situ hybridization, in vivo electroporation and neural stem cell culture.
Formation of the nervous system The nervous system arises from the early embryonic ectoderm via a choice between neural (prospective CNS) and non-neural (prospective epidermal) fates. We are use the zebrafish to dissect the molecular signaling events that underlie this choice. These studies are focused on the mechanisms by which extracellular signals results in transcriptional changes in recipient cells. Sox transcription factors play a central role in these responses. Our work focuses on the role of the Sox factors in the formation of both the central nervous system and the earlier organizer tissue from which neural inducing signals aminate.
A. Electroporation of GFP construct into placode region, followed by in situ hybridization for NeuroD gene (C)
Researchers: Cheng-Liang Kuo, Chi-Han Lam and Tom Ryder
Sox genes in neural stem cells
Once the nervous system is established, its growth is sustained by dividing cells known as 'neural stem cells'. A small number of these cells survive into adulthood and are the centre of an intense research effort to develop prospective therapeutic strategies for neurodegenerative diseases. We have been studying the expression and function of the Sox family of transcription factors in regulating the behaviour of neural stem cells for many years. Our current studies are focussed primarily on the role and mechanism of these Sox2 in maintaining these as stem cells.
Electroporation of Green Fluorescent Protein into developing spinal cord
Sox8 (red) and GFAP (green) in developing brain
References:
Shih Y-H, Dee CT, Hirst CS, Liu Y-R, Kuo CL, Laghari ZA and Scotting PJ (2010) SoxB1 factors restricts organizer formation by repressing multiple events downstream of Wnt signaling. Development 137, 2671-2681
Abelló G, Khatri S, Radosevic M, Scotting PJ, Giráldez F, Alsina B.Dev Biol. (2010) Independent regulation of Sox3 and Lmx1b by FGF and BMP signaling influences the neurogenic and non-neurogenic domains in the chick otic placode. Dev Biol. 339:166-78
Tripathi VB, Ishii Y, Abu-Elmagd MM and Scotting PJ (2009) The surface ectoderm of the chick embryo exhibits dynamic variation in its response to neurogenic signals Int J Dev Biol. 53,1023-33.
Dee CT, Hirst CS, Shih Y-H, Tripathi VB, Patient RK and Scotting PJ. (2008) Sox3 regulates both neural fate and differentiation in the zebrafish ectoderm. Dev. Biol. 320, 289-301.
Sun S-K, Dee CT, Tripathi VB, Rengifo A and Scotting PJ. (2007) Epibranchial and otic placodes are induced by a common Fgf signal, but their subsequent development is independent Dev. Biol. 303, 675-686
DEE, C.T., GIBSON, A., RENGIFO, A., SUN, S.-K., PATIENT, R.K. and SCOTTING, P.J., 2007. A change in response to Bmp signalling precedes ectodermal fate choice. International Journal of Developmental Biology, 51(1), 79-84.
SUN, S.-K., DEE, C.T., TRIPATHI, V.B., RENGIFO, A., HIRST, C.S. and SCOTTING, P.J., 2007. Epibranchial and otic placodes are induced by a common Fgf signal, but their subsequent development is independent. Developmental Biology, 303(2), 675-686.
SOTTILE, V., LI, M. and SCOTTING, P.J., 2006. Stem cell marker expression in the Bergmann glia population of the adult mouse brain. Brain Research, 1099(1), 8-17.
KORDES, U., CHENG, Y. C. and SCOTTING, P. J., 2005. Sox group E gene expression distinguishes different types and maturational stages of glial cells in developing chick and mouse.Developmental Brain Research, 157(2), 209-213.
SAVILL, R.M., SCOTTING, P.J. and COYLE, B., 2005. Strategies to investigate gene expression and function in granule cells. Cerebellum, 4(4), 271-278.
SCOTTING,P.J. and APPLEBY,V.J., 2004. Neuroembryology: How does the CNS develop and how might this inform our understanding of CNS tumors?. In:
WALKER,D.A., PERILONGO,G., PUNT,J., TAYLOR,R.E., eds. Brain and Spinal Tumours of Childhood. London: Arnold, pp. 50-66
YANG, Z-J., APPLEBY, V.J., COYLE, B., CHAN, W-I., TAHMASEB, M., WIGMORE, P.M. and SCOTTING, P.J, 2004. Novel strategy to study gene expression and function in developing cerebellar granule cells. Journal of Neuroscience Methods, 132(2), 149-160.
LEE, C. J., CHAN, W. I., CHEUNG, M., CHENG, Y. C., APPLEBY, V. J., ORME, A.T. and SCOTTING, P. J., 2002. CIC, a member of a novel subfamily of the HMG-box superfamily, is transiently expressed in developing granule neurons. Molecular Brain Research, 106(1-2), 151-156.
MONTERO, J. A., GIRON, B., ARRECHEDERA, H., CHENG, Y. C., SCOTTING, P., CHIMAL-MONROY, J., GARCIA-PORRERO, J. A. and HURLE, J. M., 2002. Expression of Sox8, Sox9 and Sox10 in the developing valves and autonomic nerves of the embryonic heart. Mechanisms of Development, 118(1-2), 199-202.
ABU-ELMAGD, M., ISHII, Y., CHEUNG, M., REX, M., LE ROUëDEC, D. and SCOTTING, P. J., 2001. cSox3 expression and neurogenesis in the epibranchial placodes. Developmental Biology, 237(2), 258-269.
CHENG, Y. C., LEE, C. J., BADGE, R. M., ORME, A. T. and SCOTTING, P. J., 2001. Sox8 gene expression identifies immature glial cells in developing cerebellum and cerebellar tumours. Molecular Brain Research, 92(1-2), 193-200.
ISHII, Y., ABU-ELMAGD, M. and SCOTTING, P.J., 2001. Sox3 expression defines a common primordium for the epibranchial placodes in chick. Developmental Biology, 236(2), 344-353.
Paediatric Brain Tumours
Brain tumours are the most common solid tumours in young children. The cure and treatment of these tumours has advanced poorly in comparison to other classes of tumour. Previously, we have studied the expression of embryonic regulatory factors in brain tumour tissue. Our current research efforts in this area are to elucidate the molecular mechanisms controlling the initiation of these tumours. In particular we are investigating the role of epigenetic alterations in triggering tumour formation from neural stem cells (Funded by Ali¹s Dream, Charlie¹s Challenge and The Children¹s Brain Tumour Research Centre). We also have a particular interest in a second group of brain tumours in children, the cranial germ cell tumours. We are studying the cellular origins and molecular mechanisms by which these tumours arise (Funded by the Samantha Dickson brain Tumour Trust and AICR). IN particular we are investigating the role of Oct4 in these tumours.
This work is funded by The Children's Brain Tumour Research Centre and the Samantha Dickson Research Trust , Ali's Dream and Charlie's Challenge.
Researchers: Dzul Azri Mohamad Noor and Chris Lee Tan
References:
Lee S-H, Jeyapalan JN, Appleby V, Noor DAM, Sottile V, and Scotting PJ (2010)Dynamic expression of Oct4 in early neural stem cells. J Anat 217, 203-213.
Lee S-H, Appleby V, Jeyapalan JN, Palmer RD, Nicholson JC, Sottile V, Gao E, Coleman N and Scotting PJ (2010) Variable methylation of the imprinted gene, SNRPN, supports a relationship between intracranial germ cell tumours and neural stem cells. J. Neuro-oncology Epub ahead of print
SCOTTING, P.J., 2006. Are cranial germ cell tumours really tumours of germ cells?. Neuropathology and Applied Neurobiology, 32(6), 569-574.
LEE, C. J., CHAN, W. I. and SCOTTING, P. J., 2005. CIC, a gene involved in cerebellar development and ErbB signaling, is significantly expressed in medulloblastomas. Journal of Neuro-Oncology, 73(2), 101-108.
SAVILL, R.M., SCOTTING, P.J. and COYLE, B., 2005. Strategies to investigate gene expression and function in granule cells. Cerebellum, 4(4), 271-278.
SCOTTING, P.J., WALKER, D.A. and PERILONGO, G., 2005. Childhood solid tumours: a developmental disorder. Nature Reviews: Cancer, 5(6), 481-488.
YANG, Z-J., APPLEBY, V.J., COYLE, B., CHAN, W-I., TAHMASEB, M., WIGMORE, P.M. and SCOTTING, P.J, 2004. Novel strategy to study gene expression and function in developing cerebellar granule cells. Journal of Neuroscience Methods, 132(2), 149-160.
LEE, C. J., APPLEBY, V. J., ORME, A. T., CHAN, W. I. and SCOTTING, P. J., 2002. Differential Expression of SOX4 and SOX11 in Medulloblastoma. Journal of Neuro-Oncology, 57(3), 201-214.
SCOTTING,P.J. and APPLEBY,V.J., 2004. Neuroembryology: How does the CNS develop and how might this inform our understanding of CNS tumors?. In:
WALKER,D.A., PERILONGO,G., PUNT,J., TAYLOR,R.E., eds. Brain and Spinal Tumours of Childhood. London: Arnold, pp. 50-66
LEE, C. J., CHAN, W. I., CHEUNG, M., CHENG, Y. C., APPLEBY, V. J., ORME, A.T. and SCOTTING, P. J., 2002. CIC, a member of a novel subfamily of the HMG-box superfamily, is transiently expressed in developing granule neurons. Molecular Brain Research, 106(1-2), 151-156.
CHENG, Y. C., LEE, C. J., BADGE, R. M., ORME, A. T. and SCOTTING, P. J., 2001. Sox8 gene expression identifies immature glial cells in developing cerebellum and cerebellar tumours. Molecular Brain Research, 92(1-2), 193-200.
GILBERTSON, R., HERNAN, R., PIETSCH, T., PINTO, L., SCOTTING, P., ALLIBONE, R., ELLISON, D., PERRY, R., PEARSON, A. and LUNEC, J., 2001. Novel ERBB4 Juxtamembrane Splice Variants Are Frequently Expressed in Childhood Medulloblastoma. GENES CHROMOSOMES AND CANCER, 31(3), 288-294.
ISHII, Y., ABU-ELMAGD, M. and SCOTTING, P.J., 2001. Sox3 expression defines a common primordium for the epibranchial placodes in chick. Developmental Biology, 236(2), 344-353.
SCOTTING, P. J., THOMPSON, S. I., PUNT, J. A. and WALKER, D. A., 2000. Paediatric brain tumours: an embryological perspective. Child's Nervous System, 16(5), 261-267.
Other Projects:
We have also collaborated with Professor Sadao Yasugi's group at the Tokyo Metropolitan University in Japan. Together, we have analysed the role of Sox genes in gut endoderm development. We have ongoing collaborations with others in Nottingham in the areas of Muscular Dystrophy and cancer
References:
CLAPP, J., MITCHELL, L.M., BOLLAND, D.J., FANTES, J., CORCORAN, A.E., SCOTTING, P.J., ARMOUR, J.A.L. and HEWITT. J.E., 2007. Evolutionary conservation of a coding function for D4Z4, the tandem DNA repeat mutated in facioscapulohumeral muscular dystrophy. American Journal of Human Genetics, 81(2), 264-279.
EL-ZAATARI, M, TOBIAS, A, GRABOWSKA, AM, KUMARI,R, SCOTTING,PJ, KAYE, P, ATHERTON, J, CLARKE, PA, POWE, DG AND WATSON, SA 2007. De-regulation of the sonic hedgehog pathway in the InsGas mouse model of gastric carcinogenesis. British Journal of Cancer.
ISHII, Y, REX, M, SCOTTING, PJ AND YASUGI, S (1998) Region specific expression of Chicken Sox2 in the developing gut and lung epithelium: regulation by epithelial-mesenchymal interactions. Dev Dynamics 213: 464-475
SAKAMOTO, N, FUKUDA, K, WATANUKI, K, KOMANO, T, SCOTTING, PJ AND YASUGI, S(2000) Role for cGATA-5 and cSox2 in transcriptional regulation of embryonic chicken pepsinogen gene by epithelial-mesenchymal interaction in developing chicken stomach. Developmental Biology 223, 103-113
MATSUSHITA, S., ISHII, Y., SCOTTING, P. J., KUROIWA, A. and YASUGI, S., 2002. Pre-Gut Endoderm of Chick Embryos Is Regionalized by 1.5 Days of Development. Developmental Dynamics, 223(1), 33-47.